Expression of cardiac alpha-actin spares extraocular muscles in skeletal muscle alpha-actin diseases--quantification of striated alpha-actins by MRM-mass spectrometry.
As with many skeletal muscle diseases, the extraocular muscles (EOMs) are spared in skeletal muscle alpha-actin diseases, with no ophthalmoplegia even in severely affected patients. We hypothesised that the extraocular muscles sparing in these patients was due to significant expression of cardiac alpha-actin, the alpha-actin isoform expressed in heart and foetal skeletal muscle. We have shown by immunochemistry, Western blotting and a novel MRM-mass spectrometry technique, comparable levels of cardiac alpha-actin in the extraocular muscles of human, pig and sheep to those in the heart. The sparing of extraocular muscles in skeletal muscle alpha-actin disease is thus probably due to greater levels of cardiac alpha-actin, than the negligible amounts in skeletal muscles, diluting out the effects of the mutant skeletal muscle alpha-actin.
Ravenscroft
Gianina
G
Centre for Medical Research, University of Western Australia and Western Australian Institute for Medical Research, B Block, Queen Elizabeth II Medical Centre, Nedlands, WA 6009, Australia.
Colley
Stephen M J
SM
Walker
Kendall R
KR
Clement
Sophie
S
Bringans
Scott
S
Lipscombe
Richard
R
Fabian
Victoria A
VA
Laing
Nigel G
NG
Nowak
Kristen J
KJ
D000199:Actins / Q000032:analysis / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D006168:Guinea Pigs; D006801:Humans; D007120:Immunochemistry; D013058:Mass Spectrometry; D018482:Muscle, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009801:Oculomotor Muscles / Q000378:metabolism*; D020033:Protein Isoforms / Q000032:analysis / Q000378:metabolism; D012756:Sheep; D013045:Species Specificity
D000199:Actins; D020033:Protein Isoforms